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An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

The patterns of how yield gaps change can suggest likely future outcomes for crop growth. This study conducts a spatial and temporal analysis of yield gaps for ten major crops from 1975 to 2010 and identifies regions where crops are experiencing ‘ceiling pressure’, signalling opportunities to improve future food security.

Automated pathotyping of synovial tissue in arthritis is a major unmet need. Here, the authors develop and demonstrate the efficacy of an automated tissue and cellular pathotyping tool for inflammatory arthritis.

Andre Berndt and colleagues introduce a machine learning approach to enhance the biophysical characteristics of genetically encoded fluorescent indicators, deriving and testing in vitro new GCaMP mutations that surpass the performance of existing fast GCaMP indicators.

Characteristic genes or proteins driving continuous biological processes are difficult to uncover from noisy single-cell data. Here, authors present DELVE, an unsupervised feature selection method to identify core molecular features driving cell fate decisions.

Chu et al. develop a monthly-calibrated photoplethysmography pipeline that leverages an implicit HbA1c with PPG signals to non-invasively estimate fasting blood glucose across three diabetic cohorts. Improved accuracy is seen over prior approaches, as assessed by mean absolute relative differences and Parkes Error Grid analyses.

The WHO targets measles elimination by 2020, a goal that relies on high vaccination coverage. Here, Takahashiet al. identify ‘coldspots’ in the African Great Lakes region where measles vaccine coverage is below 80%, suggesting that these regions should be targeted in future vaccination campaigns.

The IDG-DREAM Challenge carried out crowdsourced benchmarking of predictive algorithms for kinase inhibitor activities on unpublished data. This study provides a resource to compare emerging algorithms and prioritize new kinase activities to accelerate drug discovery and repurposing efforts.

A distribution in fin widths, due to variability in the fabrication process, can be used to study a latching condition in gallium nitride transistors in which drain current sharply transits from an off-state value to a high on-state value with a slope of less than 60 mV per decade.

Two below-threshold surface code memories on superconducting processors markedly reduce logical error rates, achieving high efficiency and real-time decoding, indicating potential for practical large-scale fault-tolerant quantum algorithms.

Forward-biased bipolar membranes (FB-BPMs), which recover potential from pH gradients through ion–ion recombination, show promise for application in sustainable devices. The authors use physics-based modeling to elucidate how ion-specific phenomena dictate performance, reveal how selective ion management can mitigate energy losses and provide insights into the rational design of next-generation FB-BPMs.

Watson et al. demonstrate that astrocyte mitochondria can be horizontally transferred to glioblastoma cells in a GAP43-dependent manner, leading to changes in mitochondrial respiration and metabolism that promote proliferation and tumor growth.

A disulfide tethering screen identified a molecule that covalently interacts with pro-apoptotic BAX at C126, inhibiting its activation.

Osteosarcomas (OS) are aggressive bone tumors which have no actionable recurrent driver mutations. Here the authors identify aberrant expression of EZHIP in a subset of OS patients as an oncogenic driver, which exhibits vulnerability to epigenetic therapies.

A representation-learning strategy for machine-learning models applied to medical-imaging tasks improves model robustness and training efficiency and mitigates suboptimal out-of-distribution performance.

A comprehensive multi-omics reference atlas of prenatal human skin shows that innate immune cells crosstalk with non-immune cells to perform pivotal roles in skin morphogenesis, including the formation of hair follicles.

Stem cell migration plays critical roles in the regeneration of adult tissue. Here, the authors demonstrate that Wnt5a-mediated activation of non-canonical Wnt signaling promotes migration of airway stem cells after epithelial injury.

The Mass Spectrometry Query Language (MassQL) is an open-source language that enables instrument-independent searching across mass spectrometry data for complex patterns of interest via concise and expressive queries without the need for programming skills.

Most aerial organs of vascular plants are covered by a waxy cuticle that limits water loss. Here the authors show that the asymmetric architecture of the cuticle creates a polarity gradient to ensure directional movement of water through olive and ivy leaf cuticles and construct bioinspired artificial membranes that mimic cuticle behaviour.

Exposure of mice to high fructose during gestation or early postnatal life causes decreased microglial phagocytosis during brain development and leads to anxiety-like behaviour in adolescence.

A quantitative morphological framework for the human thymus reveals the establishment of the lobular cytokine network, canonical thymocyte trajectories and thymic epithelial cell distributions in fetal and paediatric thymic development.

LRRC15-positive cancer-associated fibroblasts constitute a pivotal axis in tumorigenesis and are potential therapeutic targets to improve responses to immune checkpoint blockade.

Bidirectional neural interface electronic devices offer therapeutic options. Here, the authors present wafer-scale fabrication of flexible nanoporous graphene-based implantable microelectrode arrays with low impedance and high charge injection for in vivo brain recording and nerve stimulation.

Cryo-electron and atomic force microscopy shed light on how fibrils of the protein tau, which accumulate in the brain of people with Alzheimer’s disease, can be disassembled by short peptides, providing a possible route towards developing treatments.

Acyl-CoA synthetase long-chain family 4 (ACSL4)-driven changes in lipid metabolism are shown to modulate the sensitivity of intestinal epithelial cells to ferroptosis, thereby exacerbating inflammatory bowel disease.

Cascadia is a mass spectrometry-based de novo sequencing model that uses a transformer architecture to handle data-independent acquisition data and achieves substantially improved performance across a range of instruments and experimental protocols.

Soft friction remains elusive due to the complication at microscales where the elastic forces are comparable to capillarity and adhesion. Glover et al. show that a moving microparticle can induce a cease at the leading front of the underlying soft surface as a result of a build-up of compressive stress.

Focus-locking improves localization precision in single-molecule microscopy, but fiducials are often deposited at random and provide limited 3D compensation. Here, the authors fabricate 3D optical fiducials with nanometer accuracy by two-photon direct laser writing, and demonstrate isotropic 3D focus locking.

Genetic background affects how macrophages integrate multiple stimuli, e.g., to IL-4 in tissue environments. BALB/c macrophages show different transcriptional and epigenomic remodeling compared to C57BL/6, leading to distinct synergistic LPS responses.

Accessing longer-wavelength emitting organic fluorophores is critical for diagnostic imaging. Here a series of silicon-RosIndolizine fluorophores with emission maxima at 1,300 nm, 1,550 nm and 1,700 nm were synthesized. The fluorophores generate high-resolution in vivo fluorescence images in mice and establish design principles for future shortwave-infrared fluorophore designs.

The authors report PROTAC ternary complex structures involving the E3 ligase cIAP1 and target protein BTK, showing that cooperativity is not always correlated with degradation efficiency.

To be successful, selective neuromodulation requires a non-invasive method of imaging the fascicular anatomy of peripheral nerves. Here, the authors show the applicability and reliability of fast neural electrical impedance tomography for this purpose and provide its validation against the gold standards of invasive imaging.

Cold-atom interferometers have been miniaturized towards fieldable quantum inertial sensing applications. Here the authors demonstrate a compact cold-atom interferometer using microfabricated gratings and discuss the possible use of photonic integrated circuits for laser systems.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

Microelectromechanical neural probes can cause tissue damage and often cannot record from distant brain areas. Here the authors combine electrical recording, optical stimulation and microfluidic drug delivery in one multi-shank probe with thinner shanks to reduce damage and a flexible design to target long-range neural circuits.

In memory consolidation, the hippocampus has a unique way to preferentially amplify behaviour-relevant information that entails ‘replaying’ this information during periods of rest.

Here the authors show that a gene-inactivating protein complex packs inactive genes into a dynamic and accessible structure. The study challenges the traditional views that restricted accessibility and low dynamics cause gene repression.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

Jayavelu, Samaha et al., apply machine learning models on hospital admission data, including antibody titers and viral load, to identify patients at high risk for Long COVID. Low antibody levels, high viral loads, chronic diseases, and female sex are key predictors, supporting early, targeted interventions.

Nebulin-based nemaline myopathy is a heterogenous disease with unclear pathological mechanisms. Here, the authors generate a mouse model that mimics the most common genetic cause of the disease and demonstrate that muscle weakness in this model is associated with twisted actin filaments and altered tropomyosin and troponin behaviour.

AI models can extract clinical outcomes from electronic health records, but it is critical to ensure that such models preserve patient privacy. Here, the authors develop a teacher-student approach to produce shareable models for annotating cancer outcomes from imaging reports and oncologist notes while protecting patient privacy.

It is known that attention can modify the brain's representations of sensory stimuli to enhance features of importance. Here, the authors show that flexible readout of cortical representations is also required to explain the behavioral effects of attention.

A new approach for whole-genome sequencing of plasma circulating tumor DNA allows for dynamic monitoring of disease burden and ultra-sensitive detection of minimal residual disease.

While organisms like squid can adaptively modulate the optical properties of their tissues, human cells lack analogous abilities. Here the authors engineer human cells to produce protein architectures with tunable light scattering functionalities.

Nitrogen-containing compounds play an indispensable role in medicine, agriculture and materials, but alkylated derivatives especially in sterically congested environments, remain a challenge to prepare. Here, the authors report a versatile method for the regioselective hydroamination of readily available unactivated olefins with diazirines.